Insulin-like growth factor I modulates c-fos induction and astrocytosis in response to neurotoxic insult

Fernández, Adolfo; Garcı́a-Estrada, Joaquı́n; Garcia-Segura, Luis Miguel; Torres‐Alemán, Ignacio

doi:10.1016/s0306-4522(96)00395-8

Cited by 41 publications

(30 citation statements)

References 31 publications

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“…It has a specificity Ͻ1% cross-reactivity with either insulin or IGF-II, as determined by competition with 125 I-IGF-1 (Carro et al, 2000). Also the IGF-1 receptor antagonist known as JB-1 has been shown by the Torres-Aleman group and others to inhibit the action of IGF-1 both in vivo and in vitro (Fernandez et al, 1997). Bound antibodies were detected by incubating sections with biotinylated goat anti-rabbit IgG (1:200; catalog #BA-1000; Vector Laboratories) followed by fluoresceinconjugated extravidin (1:300; E2761; Sigma).…”

Section: Methodsmentioning

confidence: 99%

Setting the Pace for Retinal Development: Environmental Enrichment Acts Through Insulin-Like Growth Factor 1 and Brain-Derived Neurotrophic Factor

Landi

Ciucci²,

Maffei³

et al. 2009

J. Neurosci.

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Environmental enrichment strongly affects visual system maturation both at retinal and cortical levels. Which molecular pathways are activated by an enriched environment (EE) to regulate visual system development has not been clarified. Here, we show that early [postnatal day 1 (P1) to P7] insulin-like growth factor 1 (IGF-1) injections in the eyes of non-EE rat pups mimic EE effects both in increasing BDNF levels in the retinal ganglion cell layer at P10 and in determining a more adult-like retinal acuity, assessed with pattern electroretinogram at P25. Blocking IGF-1 action in EE animals during the same early postnatal time window by injecting the IGF-1 receptor antagonist JB1 prevents EE effects both on BDNF expression and on retinal acuity maturation. Reducing BDNF expression in the retina of IGF-1-treated rats prevents IGF-1 effects on retinal acuity development. Finally, we show that tyrosine hydroxylase (TH) expression is increased in the retina of P10 EE and IGF-1-treated rats and that blocking TH expression in EE animals prevents EE from affecting retinal acuity development. Thus, early levels of IGF-1 play a key role in mediating EE effects on retinal development through an action that requires BDNF and involves dopaminergic amacrine cell network.

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Section: Methodsmentioning

confidence: 99%

Setting the Pace for Retinal Development: Environmental Enrichment Acts Through Insulin-Like Growth Factor 1 and Brain-Derived Neurotrophic Factor

Landi

Ciucci²,

Maffei³

et al. 2009

J. Neurosci.

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“…A common feature in these cases of neurodegeneration is a depletion of IGF-I levels in both serum and brain tissue. In addition, changes in endogenous IGF-I input by diverse experimental approaches modulate the response of the cerebellum to deafferentation (7). These data strongly suggest that neuronal death in the cerebellum, and possibly in other areas also (8), is related to deficits of IGF-I neurotrophic input.…”

mentioning

confidence: 85%

Insulin-like growth factor I restores motor coordination in a rat model of cerebellar ataxia

Fernández

Vega

Torres‐Alemán

1998

Proc. Natl. Acad. Sci. U.S.A.

152

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We tested the potential of insulin-like growth factor I (IGF-I) to induce functional recovery in an animal model of cerebellar ataxia because this motor impairment is accompanied in humans and rodents by distinct changes in several components of the IGF-I trophic system. Rats rendered ataxic by deafferentation of the cerebellar cortex with 3-acetylpyridine recovered motor function after IGF-I was administered, as determined by behavioral and electrophysiological tests. When treated with IGF-I, inferior olive neurons, the targets of the neurotoxin, were rescued to various degrees (from 92 to 27% of surviving neurons), depending on the time that treatment with IGF-I was initiated. Furthermore, full recovery was obtained regardless of the route by which the trophic factor was administered (intraventricular or subcutaneous) even in rats with severe neuronal loss. These results suggest that human ataxia could be treated with IGF

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“…Moreover, in the GT1-7 neuronal line, IGF-I-mediated neuroprotection against oxidative stress is associated with activation of NFB (14). However, in glial cells where NFB mediates the action of proinflammatory cytokines (15,16), IGF-I reduces glial inflammation after brain injury (8). Based on this apparent biological contradiction, we postulated that IGF-I might differentially regulate the NFB pathway in astrocytes as compared with neurons.…”

Section: Igf-i Induces Transitory Dephosphorylation Of Serine In Ib␣-mentioning

confidence: 97%

“…In vivo, IGF-I protects neurons against a variety of brain insults typically associated with overproduction of proinflammatory cytokines such as stroke, brain trauma, and multiple sclerosis (6,7). Moreover, IGF-I therapy dramatically reduces reactive astrocytosis following neuronal damage in the cerebellum (8), presumably by limiting the glial reaction and the progression of inflammation. Thus, it is likely that the benefits obtained by IGF-I treatment in these pathological conditions results from its direct action on neuronal survival and an inhibition of the glial inflammatory reaction.…”

mentioning

confidence: 99%

Insulin-like Growth Factor-I Stimulates Dephosphorylation of IκB through the Serine Phosphatase Calcineurin (Protein Phosphatase 2B)

Pons

Torres‐Alemán

2000

Journal of Biological Chemistry

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Astrocytes represent the most abundant cell type of the adult nervous system. Under normal conditions, astrocytes participate in neuronal feeding and detoxification. However, following brain injury, local increases in inflammatory cytokines trigger a reactive phenotype in astrocytes during which these cells produce their own inflammatory cytokines and neurotoxic free radicals. Indeed, progression of this inflammatory reaction is responsible for most neurological damage associated with brain trauma. Insulin-like growth factor-I (IGF-I) protects neurons against a variety of brain pathologies associated with glial overproduction of proinflammatory cytokines. Here, we demonstrate that in astrocyte cultures IGF-I regulates NFB, a transcription factor known to play a key role in the inflammatory reaction. IGF-I induces a site-specific dephosphorylation of IB␣ (phospho-Ser 32 ) in astrocytes. Moreover, IGF-I-mediated dephosphorylation of IB␣ protects this molecule from tumor necrosis factor ␣ (TNF␣)-stimulated degradation; therefore, IGF-I also inhibits the nuclear translocation of NFB (p65) induced by TNF␣ exposure. Finally, we show that dephosphorylation of IB␣ by IGF-I pathways requires activation of calcineurin. Activation of this phosphatase is independent of phosphatidylinositol 3-kinase and mitogen-activated protein kinase. Thus, these data suggest that the therapeutic benefits associated with IGF-I treatment of brain injury are derived from both its positive effects on neuronal survival and inhibition of the glial inflammatory reaction.Based on morphology and physiology, the adult nervous system is composed of two main groups of cells, neurons and glia. Neurons transmit high speed information through depolarization potentials, whereas glial cells provide a basic support to neurons. Under normal conditions, glial cells, and in particular astrocytes, modulate neuronal feeding and detoxification and produce neuronal survival factors. However, following brain injury, astrocytes actively participate in the inflammatory response and in scar formation. Inflammatory cytokines resulting from brain insults induce astrocytes to adopt a reactive phenotype during which these cells also produce proinflammatory cytokines and neurotoxic free radicals such as nitric oxide (1). Reactive astrocytes produce a compendium of inflammatory and anti-inflammatory cytokines; the balance between these opposing groups of factors determines the fate of the affected neurons. Proinflammatory factors such as tumor necrosis factor ␣ (TNF␣) 1 or interleukin 1 (IL-1) trigger the expression of more proinflammatory genes in astrocytes and eventually induce apoptosis in neurons, whereas other factors including interleukin 4 (IL-4) and insulin-like growth factor I (IGF-I) reduce inflammation and promote survival of neurons (2). Cross-talk between the signaling pathways of these two groups of factors has been proposed as a mechanism for regulation of apoptosis and survival. Although it has been known for many years that TNF␣ induces insulin resistance...

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Insulin-like growth factor I modulates c-fos induction and astrocytosis in response to neurotoxic insult

Cited by 41 publications

References 31 publications

Setting the Pace for Retinal Development: Environmental Enrichment Acts Through Insulin-Like Growth Factor 1 and Brain-Derived Neurotrophic Factor

Setting the Pace for Retinal Development: Environmental Enrichment Acts Through Insulin-Like Growth Factor 1 and Brain-Derived Neurotrophic Factor

Insulin-like growth factor I restores motor coordination in a rat model of cerebellar ataxia

Insulin-like Growth Factor-I Stimulates Dephosphorylation of IκB through the Serine Phosphatase Calcineurin (Protein Phosphatase 2B)

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